title: Effects of agomelatine on oxidative stress in the brain of mice after chemically induced seizures.
abstract: Agomelatine is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties. We analyzed whether agomelatine has antioxidant properties. Antioxidant activity of agomelatine (25, 50, or 75 mg/kg, i.p.) or melatonin (50 mg/kg) was investigated by measuring lipid peroxidation levels, nitrite content, and catalase activities in the prefrontal cortex, striatum, and hippocampus of Swiss mice pentylenetetrazole (PTZ) (85 mg/kg, i.p.), pilocarpine (400 mg/kg, i.p.), picrotoxin (PTX) (7 mg/kg, i.p.), or strychnine (75 mg/kg, i.p.) induced seizure models. In the pilocarpine-induced seizure model, all dosages of agomelatine or melatonin showed a significant decrease in TBARS levels and nitrite content in all brain areas when compared to controls. In the strychnine-induced seizure model, all dosages of agomelatine and melatonin decreased TBARS levels in all brain areas, and agomelatine at low doses (25 or 50 mg/kg) and melatonin decreased nitrite contents, but only agomelatine at 25 or 50 mg/kg showed a significant increase in catalase activity in three brain areas when compared to controls. Neither melatonin nor agomelatine at any dose have shown no antioxidant effects on parameters of oxidative stress produced by PTX- or PTZ-induced seizure models when compared to controls. Our results suggest that agomelatine has antioxidant activity as shown in strychnine- or pilocarpine-induced seizure models.
authors.affiliation: School of Medicine, University of Fortaleza (UNIFOR)/RENORBIO, Rua Desembargador Floriano Benevides Magalhães, 221 3º Andar, Fortaleza, Ceará, 60811-690, Brazil. claytonaguiar@hotmail.com
authors.forename: Carlos Clayton Torres
authors.initials: CC
authors.lastname: Aguiar
authors.forename: Anália Barbosa
authors.initials: AB
authors.lastname: Almeida
authors.forename: Paulo Victor Pontes
authors.initials: PV
authors.lastname: Araújo
authors.forename: Germana Silva
authors.initials: GS
authors.lastname: Vasconcelos
authors.forename: Edna Maria Camelo
authors.initials: EM
authors.lastname: Chaves
authors.forename: Otoni Cardoso
authors.initials: OC
authors.lastname: do Vale
authors.forename: Danielle Silveira
authors.initials: DS
authors.lastname: Macêdo
authors.forename: Luzia Kalyne Almeida Moreira
authors.initials: LK
authors.lastname: Leal
authors.forename: Glauce Socorro
authors.initials: GS
authors.lastname: de Barros Viana
authors.forename: Silvânia Maria Mendes
authors.initials: SM
authors.lastname: Vasconcelos
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D002374:Catalase / Q000378:metabolism; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole; D010852:Picrotoxin; D010862:Pilocarpine; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D013331:Strychnine; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D002374:Catalase; D009573:Nitrites; D010433:Pentylenetetrazole; D010852:Picrotoxin; D010862:Pilocarpine; D013331:Strychnine; C084711:agomelatine; D009281:Naphthalenes